In Reply Dr Karayiannis and colleagues raise 3 important points regarding our results. Adjusting for baseline aspirin use does not change the estimated treatment effect for the primary outcome (HR, 0.64; 95% CI, 0.49-0.83), nor do we observe any evidence of an interaction with intensive blood pressure control (P = .98). In terms of serious adverse events, regardless of frailty status, there were no differences in overall serious adverse events when ascertained using protocol-based standard interviews at specified intervals. However, for specific events assigned by clinicians as being possibly or definitely related to the intervention, the result in participants aged 75 years or older parallels the result from the primary SPRINT publication. In the intensive treatment group, 89 (6.8%) experienced such an event compared with 47 (3.6%) in the standard treatment group (HR, 1.93; 95% CI, 1.34-2.76). However, because treatment assignment was not blinded to clinicians and participants were also specifically warned about the possible occurrence of these conditions, intervention-related serious adverse events may have been overreported in the intensive group. Karayiannis and colleagues are also correct that this same observation is true for the frail subgroup.